Gynecologic Malignancies in Older Women

ABSTRACT: The aging of the population is a social phenomenon that will
present a challenge to clinical practice in the 21st century. Women constitute a
majority of the elderly population as they outlive males by 5 to 7 years.
Ovarian, endometrial, and vulvar cancers are diseases seen more commonly in
postmenopausal and elderly women. Cervical cancer continues to be a significant
problem in the elderly and is usually detected at a later stage in that
population than in younger patients. Accordingly, primary care clinicians ought
to possess a thorough knowledge of gynecologic malignancies and should refer
women who present with these disorders to a gynecologic oncologist. Ovarian
cancer patients treated by a gynecologic oncologist are more likely to undergo
proper surgical staging, leading to optimal debulking surgery and improved
survival. Age, by itself, should not alter the diagnostic and therapeutic
approach to gynecologic malignancy. Elderly patients can safely undergo radical
pelvic surgery. Multiagent chemotherapy is also possible in the elderly without
excess morbidity, and without compromise of response rates. Radiation therapy
for cervical cancer appears to be as effective and is generally well tolerated.
The Papanicolaou (Pap) test continues to be the primary screening tool for
cervical cancer. Although transvaginal ultrasound seems to be useful in
detecting early-stage ovarian cancer, its cost effectiveness for screening the
general population remains to be demonstrated. The main considerations in the
treatment of ovarian, endometrial, cervical, and vulvar cancer are discussed. [ONCOLOGY
15(5):580-598, 2001]

The 20th century has witnessed
the aging of a significant portion of the population, with major changes in the social structure, particularly
in developed countries. The world’s elderly population is growing at a rate of
2.4% per year.[1] Sweden has the highest proportion of elderly, with 17.5% of
its population aged 65 years and older in 1997. This age shift is the result of
reduced birth rates, improvements in health and nutrition, and increased
longevity.

The aging population has a direct effect on health-care delivery
because it is associated with new disease patterns as well as transitions in
economic, social, and even ethical issues. Medical policy makers are calling for
health promotion and disease prevention initiatives aimed at the population
older than 50 years.[2]

The concept of "elderly" seems to be an inadequate
generalization that covers a wide range of years as well as a diverse population
from the personal and social points of view. Age definitions are relevant in
gynecologic oncology because ovarian, endometrial, and vulvar cancers tend to be
diseases of "older" women in their postmenopausal years. Elderly women
are usually defined as being more than 70 to 75 years of age in the few studies
that address this particular issue. Women older than age 80 to 85 years are
considered the "old-old" or "very old." This group comprises
22% of the overall elderly population in developed countries.

As baby boomers born between 1945 and 1964 enter menopause, they
will have a direct effect on clinical practice. By the year 2010, the number of
postmenopausal women will exceed the number of women of reproductive age for the
first time in the history of the United States.[3] On average, in developed
countries, women outlive men by 5 to 7 years. According to the United States
Bureau of the Census in 1997, the life expectancy of a female at birth was 79.5
years vs 72.8 years for a male. Women account for about two-thirds of the
population aged 75 years and older, and the number of women aged 85 or older is
expected to double between 2030 and 2050.[4]

The risk of developing a gynecologic tumor is highest in elderly
women. When compared with women aged 40 to 65 years, those over age 65 have a
higher risk of developing cancer of the uterus (twofold), ovaries (threefold),
and cervix (10% increased risk).[5] There is also an increased risk of
cancer-related death in elderly women that seems to be independent of the
increased incidence. One possible explanation is related to stage of disease.
Ovarian, endometrial, and cervical cancers tend to be diagnosed at a more
advanced stage in elderly women.[6,7] Biological differences are possible, but
other factors, including decreased screening, have been reported.[8-10]

Elderly women fail to undergo routine gynecologic examinations
and screening procedures.[8,9,11] Even in the presence of symptoms, Kennedy and
colleagues found the diagnosis of cancer delayed by 8.3 months and no previous
pelvic examination performed for an average of 4.5 years.[11] Although women’s
awareness of health problems appears to be increasing, preventive screening
rates do not seem to be changing accordingly. A recent survey found that 66% of
all respondents said they had undergone a clinical breast examination and
Papanicolaou (Pap) smear within the previous year.[12]

Many barriers to compliance with cancer screening procedures
exist, including socioeconomic, cultural, and educational factors as well as
physician attitudes.[13] After age 65 years, the number of medical office visits
decreases by about half when compared to women aged 45 to 64 years (7.3% vs
13.6%).[14] Thus, any physician visit should be taken as a major opportunity to
educate patients and offer screening services. Physician recommendation is a
major predictor of compliance with screening tests.[15]

CERVICAL CANCER

The Pap Test: The Pap test continues to be the gold standard
screening test for cervical carcinoma. Implementation of Pap testing is
considered to be the main reason for the decrease in the incidence and mortality
of cervical carcinoma in women in the United States, with two exceptions: older
women and black women. Women over age 65 years have the highest percentage of
late-stage cervical cancer at diagnosis regardless of race or ethnic
background.[16,17] Most patients diagnosed with invasive cervical carcinoma have
not had a recent Pap test,[18] even at early stages of the disease.[19]

The false-negative rate of Pap smears is about 20%. Sampling
errors contribute greatly to the incidence of false-negative tests. Recession of
the squamocolumnar junction in postmenopausal patients results in limited
sampling of cells. Cervical stenosis resulting from atrophy also limits sampling
of the transformation zone.[20]

HPV Testing: Human papillomavirus (HPV) testing with the
Hybrid Capture II has proven to be a sensitive marker for detecting dysplasia in
the presence of a minimally abnormal Pap test result.[21] Persistent HPV
infection has been associated with a higher risk of cervical carcinoma.[22] The
rate of HPV positivity and distribution of HPV types has been found to be
similar between tumors developing in younger and older patients.[23]

In a population-based study, the prevalence of high-grade
squamous intraepithelial lesions was found to have a bimodal distribution with
peaks at age 30 and 65 years and older. Human papillomavirus was found in 89% of
high-grade squamous intraepithelial lesions and 88% of cancers.[24] One of the
likely general screening applications for HPV DNA testing would be the
evaluation of mildly abnormal Pap tests with atypical squamous cells of
undetermined significance (ASCUS). This application would also be valid for
older women.[25]

OVARIAN CANCER

Screening methods for ovarian cancer continue to be
investigated. Early diagnosis is difficult because of lack of symptoms and the
difficulty of detecting small adnexal masses on pelvic examination.
Three-quarters of patients have stage III and IV disease at the time of initial
diagnosis. Symptoms in the months preceding diagnosis are nonspecific and
include bloating, abdominal pain, frequent indigestion, a feeling of fullness,
and fatigue.

CA-125 Screening: CA-125 is the most extensively studied
antigen associated with ovarian cancer. A normal value is generally considered
to be 35 U/mL or less. CA-125 is elevated in 90% of women with stage III
and IV ovarian cancer, but in only 50% of women with stage I disease. The test
has a low specificity because the level of the antigen may be elevated in other
pelvic and gastrointestinal malignancies as well as in benign conditions,
including endometriosis, pelvic inflammatory disease, pregnancy, and
leiomyomas.[26] Therefore, CA-125 has no application for screening of the
general population.

The role of CA-125 as a screening tool in postmenopausal women
was evaluated in a study conducted at the Royal London Hospital. This
prospective study of 22,000 postmenopausal women used serum CA-125 measurements
as a primary screening method for ovarian cancer.[27] Although the test was
associated with high specificity (98%), for each case of ovarian cancer
diagnosed, 50 false-positives occurred. Further analysis of the data
demonstrated that elevation of CA-125 over 100 U/mL significantly increases the
relative risk of developing an index cancer.[28]

Transvaginal Ultrasonography: Much effort has been dedicated
to the evaluation of transvaginal ultrasonography as a screening tool for
ovarian cancer. The potential success of sonography is based on its ability to
detect early morphologic changes that cannot be detected by examination. Because
stage I disease has an excellent 5-year survival (approximately 90%), requires
less radical surgery, and often does not require adjuvant chemotherapy, any
intervention that can accurately detect early-stage disease would have the
greatest effect on outcomes.

Morphologic scoring systems have been developed to increase the
specificity of transvaginal ultrasound. The most reliable criteria are ovarian
size or volume, presence of papillary projections, and cyst complexity.
Papillary projections correlate highly with malignancy.[29] A recent report from
a large study defined the utility of ultrasound in detecting ovarian cancer in
asymptomatic women.[30] Annual transvaginal ultrasound was performed in 14,469
asymptomatic women aged 50 years and over and in women with a family history of
ovarian cancer aged 25 and older. As expected, a large number of ultrasounds
(57,214) had to be performed in order to detect a few ovarian cancers.[11] The
sensitivity of the screening was 81% and the specificity was 98.9%.

On the other hand, it was possible to detect early-stage disease
in 72% of the cancers identified. A survival advantage was also demonstrated. In
screened patients, the 5-year survival for epithelial cancer was 86.6% vs 50% in
unscreened patients. Although color Doppler imaging may reduce the
false-positive rate in ovarian cancer detection, its utility as a primary
screening tool is limited, and the expenses are significant.